In this project, we test the hypothesis that treatment with 1-isoproterenol may enhance toxicity by decreasing the "average total body clearance" of many compounds, including drugs, that are not metabolized significantly and are excreted rapidly and almost entirely in urine. 1-Isoproterenol (0.3 mg base/kg, s.c. administered within 10 sec of the i.v. injection of a labeled compound) reduced by 30 to 70% the "average total body clearance" of the following 14C-labeled compounds: inulin, p-aminohippuric acid, N-methylnicotinamide, tetraethylammonium bromide, decamethonium bromide, hexamethonium dichloride, and penicillin. Salbutamol also decreased the "average total body clearance" of hexamethonium by about 70%. Treatment with 1-isoproterenol decreased by 40 to 66% the LD50 values for pentamethonium, hexamethonium, decamethonium, and tetramethylammonium and by 20% that of tetraethylammonium. These effects can be explained by an apparent decrease in the glomerular filtration rate and a reduced renal plasma flow or by a reversible decrease in the number of functioning nephrons.